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Multi-analytic approach to the understanding of the patho-physiology of retinitis pigmentosa and related diseases using genetic, immunologic and clinical imaging methods

利用遗传、免疫学和临床成像方法的多重分析方法来了解色素性视网膜炎及相关疾病的病理生理学

基本信息

批准号：
17591831
负责人：
MANDAI Michiko
金额：
$ 2.24万
依托单位：
RIKEN (2006)Kyoto University (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

To gain insight into the detailed patho-physiology of retinitis pigmentosa (RP), retinal degenerative disease with rod photoreceptor loss, we studied 250 patients with typical RP using genetic, immunologic and clinical imaging analysis. First of all, we established the labor-and cost efficient genetic diagnostic system using WAVE d-HPLC system (Transgenomic co.). The system enabled us to screen for 29 reported causal genes of RP followed by direct sequencing to confirm the presence of specific gene mutation. Although we collected the patients regardless their familial background, among the 250 patients tested, we detected possible causal gene alteration in 30 patients. This frequency is as high as the frequency of known gene mutation among autosomal dominant RP patients alone which is considered to give the highest detection frequency. In our study, RHO, RDS, FSCN were the most frequent candidates as causal genes, which was compatible with previous reports in Japan, indicating the prac … More ticality of our gene diagnostic system. The relevance of novel gene alterations detected in our study and the disease should be further evaluated. We then tested the serum antibody titer against recoverin in RP patients to check the autoimmunity against self-retinal antigen using ELISA. In many RP patients, anti-recoverin antibody titer was increased compared to that in patients with age-related macular degeneration. Some of the patients with high antibody titer showed visual field loss unproportinal to the retinal atrophy area, and some of these patients had had a period of transient and rapid worsening of the disease in their disease history. These indicated a possible involvement of autoimmune reaction secondary to retinal degeneration in the course of RP progress. We also evaluated the photoreceptor status (i.e. loss of outer segment) in RP patients using optical coherent tomography (OCT) and retinal auto-fluorescence which is considered to indicate the well-functioning retinal pigment epithelial cells (RPEs). The area of functional photoreceptors and that of functional RPEs did not correspond in some patients, indicating that in some patients, there is a discrepancy between the time of photoreceptor degeneration and that of RPE deterioration, although they make a concomitant complex. Less

为了深入了解色素性视网膜炎（RP）的详细病理生理学，我们对250例典型RP患者进行了遗传学、免疫学和临床影像学分析。首先，我们利用WAVE d-HPLC系统（Transgenomic co.）建立了省力、省钱的基因诊断系统。该系统使我们能够筛选29个报道的RP致病基因，然后直接测序以确认特定基因突变的存在。虽然我们收集的患者不考虑他们的家庭背景，但在250名患者中，我们在30名患者中发现了可能的因果基因改变。这一频率与常染色体显性RP患者中已知基因突变的频率一样高，被认为是最高的检测频率。在我们的研究中，RHO、RDS、FSCN是最常见的致病基因，这与日本先前的报道相一致，表明我们的基因诊断系统的实用性。在我们的研究中发现的新基因改变与疾病的相关性应该进一步评估。采用ELISA法检测RP患者血清抗恢复抗体滴度，检测RP患者对自身视网膜抗原的自身免疫。在许多RP患者中，与年龄相关性黄斑变性患者相比，抗恢复抗体滴度增加。部分抗体滴度高的患者出现与视网膜萎缩区不相符的视野丧失，部分患者在病史中曾有过一段短暂而迅速的病情恶化。这些提示在RP进展过程中可能涉及继发于视网膜变性的自身免疫反应。我们还利用光学相干断层扫描（OCT）和视网膜自身荧光技术评估了RP患者的光感受器状态（即外节缺失），这被认为是功能良好的视网膜色素上皮细胞（RPEs）的指示。部分患者的功能性光感受器面积与功能性RPE面积不对应，说明部分患者的光感受器变性时间与RPE变性时间存在差异，虽然两者是并存的复合体。少

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pigment epithelial detachment in polypoidal choroidal vasculopathy

DOI：
10.1016/j.ajo.2006.08.025
发表时间：
2007-01-01
期刊：
AMERICAN JOURNAL OF OPHTHALMOLOGY
影响因子：
4.2
作者：
Tsujikawa, Akitaka;Sasahara, Manabu;Yoshimura, Nagahisa
通讯作者：
Yoshimura, Nagahisa

Polypoidal choroidal vasculopathy with choroidal vascular hyperpermeability

DOI：
10.1016/j.ajo.2006.05.051
发表时间：
2006-10-01
期刊：
AMERICAN JOURNAL OF OPHTHALMOLOGY
影响因子：
4.2
作者：
Sasahara, Manabu;Tsujikawa, Akitaka;Yoshimura, Nagahisa
通讯作者：
Yoshimura, Nagahisa

A new PCR-based approach for the preparation of RNA probe.

一种新的基于 PCR 的 RNA 探针制备方法。

DOI：
发表时间：
2005
期刊：
J Biochem Biophys Methods 62
影响因子：
0
作者：
H. Tsukitome;K. Ikesugi;K. Matsunaga;M. Sasoh;Y. Uji;Y. Uji;Yukitaka Uji;川越直顕;Tsujikawa A. et al.;Kawagoe N. et al.;Tsujikawa A et al.;Gotho N. et al.;Sasahara M. et al.;Suzuki T. et al.;Gotho N. et al.;Sasahara M. et al.;Suzuki T. et al.;Sasahara M et al.;Suzuki T. et al.;Suzuki T
通讯作者：
Suzuki T

Is Removal of Internal Limiting Membrane always Necessary during Stage 3 Idiopathic Macular Hole

特发性黄斑裂孔第 3 阶段是否必须去除内界膜

DOI：
发表时间：
2005
期刊：
Retina 25
影响因子：
0
作者：
H. Tsukitome;K. Ikesugi;K. Matsunaga;M. Sasoh;Y. Uji;Y. Uji;Yukitaka Uji;川越直顕;Tsujikawa A. et al.;Kawagoe N. et al.;Tsujikawa A et al.;Gotho N. et al.;Sasahara M. et al.;Suzuki T. et al.;Gotho N. et al.;Sasahara M. et al.;Suzuki T. et al.;Sasahara M et al.;Suzuki T. et al.;Suzuki T;Kimura T
通讯作者：
Kimura T

Iris-derived cells from adult rodents and primates adopt photoreceptor-specific phenotypes